Aloe vera is a medicinal plant renowned for its diverse therapeutic properties, including anti-inflammatory, antioxidant, antimicrobial, wound-healing, and antidiabetic effects. Its bioactive compounds, such as anthraquinones (e.g., aloin, aloe-emodin) and polysaccharides (e.g., acemannan), contribute to its efficacy in treating digestive disorders, diabetes, skin conditions, cardiovascular diseases, and even cancer. However, the concomitant use of Aloe vera with conventional medications raises concerns about herb-drug interactions, particularly those involving the cytochrome P450 (CYP450) enzyme system. Key compounds like aloe-emodin and emodin can inhibit CYP1A2 and CYP3A4, potentially altering the metabolism of drugs such as clopidogrel and methadone, leading to toxicity or even therapeutic failure depending on the drug affected. This chapter highlights the dual role of Aloe vera as both a therapeutic agent and a source of potential drug interactions, emphasizing the need for careful clinical monitoring to ensure safe and effective use in polypharmacy regimens.